ADAMTS3

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene is the major procollagen II N-propeptidase.^[6]

Because of the high similarity to ADAMTS2, the major substrate of ADAMTS3 had been erroneously assumed to be procollagen II.^[7] However, ADAMTS3 appears largely irrelevant for collagen maturation but instead is required for the activation of the lymphangiogenic growth factor VEGF-C.^[8] Hence, ADAMTS3 is essential for the development and growth of lymphatic vessels. The proteolytic processing of VEGF-C by ADAMTS3 is regulated by the CCBE1 protein.

ADAMTS3 has been shown to cleave reelin, a protein that regulates the proper lamination of the brain cortex and whose signal activity is found to be disrupted in a number of neuropsychiatric conditions.^[9]

A deficiency of this protein may be responsible for dermatosparaxis, a genetic defect of connective tissues.^[6]

Some hereditary forms of lymphedema are caused by mutations in ADAMTS3.^[10][11]